Although the cost of treating newly diagnosed patients with multiple myeloma is greatly increased with the use of 3 drugs, 2-drug regimens should no longer be considered adequate, according to new data presented at ASH 2015.
The use of triplet therapies with a proteasome inhibitor, an immunomodulatory drug (IMiD), and a steroid has been growing in the United States, and lenalidomide (Revlimid) was approved in 2015 for first-line treatment.
The phase 3 SWOG S0777 trial, which was reported by Brian G.M. Durie, MD, Hematologist/Oncologist, Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, compared the regimen of lenalidomide, bortezomib (Velcade), and low-dose dexamethasone (VRd) with lenalidomide plus dexamethasone (Rd). Both arms received maintenance Rd until disease progression or unacceptable toxicity. VRd significantly improved response rates, progression-free survival (PFS), and overall survival (OS).
“VRd induction followed by continuous Rd is a potential new standard of care,” Dr Durie reported.
Sagar Lonial, MD, Chief Medical Officer, Emory University’s Winship Cancer Institute, Atlanta, said that the results solidify the use of 3 drugs as the optimal first-line therapy. A triplet containing a proteasome inhibitor, an IMiD, and a steroid has “come of age” as the standard of care, he said.
All Outcomes Improved
The SWOG S0777 trial randomized 525 patients to VRd or to Rd, and the patients were offered maintenance Rd.
The overall response rates were 81.5% with VRd and 71.5% with Rd, which included complete responses in 15.7% and 8.4% of the patients, respectively. The median PFS was 43 months with VRd and 31 months with Rd (hazard ratio [HR], 0.71; one-sided P = .001). The median OS was 75 months versus 64 months, respectively (HR, 0.70; two-sided P = .025).
The regimens were generally well-tolerated, although grade ≥3 toxicity was more common with VRd than with Rd, including neurologic events (33% vs 11%, respectively), pain (12% vs 4%), sensory toxicity (23% vs 3%), and gastrointestinal side effects (22% vs 8%).
Dr Durie pointed out that bortezomib was administered intravenously twice weekly, which was the way it was typically administered in 2008 when the study began. Subcutaneous or less frequent administration of bortezomib might have ameliorated some of the toxicity, he suggested.
According to Dr Lonial, “We have now established that a 3-drug induction of an IMiD and a proteasome inhibitor is the best combination. Three drugs are better than 2, with the exception of frail patients.”